On June 2, 2014 Bayer reported that it has entered into a global agreement with Orion for the development and commercialization of the compound ODM-201, an investigational novel oral androgen receptor inhibitor (Press release Orion Pharma, JUN 1, 2014, View Source [SID:1234500614]). ODM-201 is in clinical development for the treatment of patients with prostate cancer. Bayer and Orion plan to start jointly the clinical Phase III program to further evaluate the efficacy and safety of ODM-201 in patients with non-metastatic castration-resistant prostate cancer (nm-CRPC) in 2014. These patients are at high risk of developing metastatic disease and can be identified due to rapid Prostate Specific Antigen (PSA) increases.

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"We see in ODM-201 a potential new treatment for patients with high risk non-metastatic castration-resistant prostate cancer and are looking forward to developing this promising compound," said Dr. Joerg Moeller, Member of the Bayer HealthCare Executive Committee and Head of Global Development. "Bayer’s oncology portfolio currently includes Xofigo which has been shown to prolong life in patients with castrate resistant prostate cancer with symptomatic bone metastases, and no known visceral metastases. From a clinical perspective, ODM-201 has the potential to complement our portfolio in prostate cancer and enables us to deliver new treatment options for patients who desperately need them."

"Joining forces with Bayer, I believe that we have again achieved a collaboration that represents the best of all worlds," said Dr. Reijo Salonen, SVP R&D and Chief Medical Officer for Orion. "Bayer has recently committed to developing therapies in Oncology, particularly for prostate cancer. At Orion, we continue our track record of inventing innovative molecules. And most importantly, for patients with prostate cancer, this partnership will bring a medicine that will make an important difference to their lives."

Under the terms of the agreement, Bayer and Orion will jointly develop ODM-201, with Bayer contributing a major share of the costs of future development. Bayer will commercialize ODM-201 globally and Orion has the option to co-promote ODM-201 in Europe. Orion will be responsible for the manufacturing of the product. Orion will receive an upfront payment of EUR 50 million and is eligible to receive cash payments from Bayer upon achievement of certain development, tech transfer and commercialization milestones, as well as tiered double-digit royalties on future global net sales. Orion will use the majority of the up-front payment this year against the costs of the Phase III study to be started this year.

On June 1, 2014 (Taipei) TS-1 Capsule (Taiwan Capsule), a chemotherapeutic drug from Taiwan’s Toyo Pharmaceutical (4105: TW), reported that it has recently been listed in the "National Health Insurance Drug Benefits Project" after receiving an indication for advanced pancreatic cancer in August 2013 (Press release, TTY Biopharm, JUN 1, 2014, View Source;ai-si-mo—-huo-wan-ji-yi-zang-ai-zhi-jian-bao-gei-fu [SID1234526668]). The payment standard jointly drafted the resolution of the meeting and agreed to include the national health insurance drug payment. The payment was made to patients who were unable to undergo surgical resection or metastatic pancreatic cancer in the late stage of treatment, and took effect on June 1, 2014. TS-1 Capsule was originally developed by Japan Dapeng Pharmaceutical Industry Co., Ltd. and was authorized to develop and market this drug in Taiwan’s Toyo Pharmaceuticals in Taiwan.

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Taiwanese pancreatic cancer has shown significant growth in recent years. According to the latest data released by the Department of Health and Welfare, there were 1,827 new patients with pancreatic cancer in the 100 years of the Republic of China, and 1,607 patients died of pancreatic cancer, which ranks among the top ten causes of cancer in the country. Eight people ranked a little more than 99 years ago in the Republic of China, showing that the current treatment is not effective. Most pancreatic cancers are diagnosed at the late stage when the tumor cannot be surgically removed. The patient needs to receive systemic chemotherapy. However, the survival time of advanced pancreatic cancer is extremely short, and the choice of drugs is limited, and patients need urgently more effective treatment options.

Mr. Lin Rongjin, General Manager of Taiwan’s Toyo Pharmaceutical Co., Ltd., said: "Continuously cultivating medicines in the field of cancer has always been the goal of Taiwan’s East Sample. This breakthrough will benefit more cancer patients. It is a good news." Taiwan’s Toyo Pharmaceutical Co., Ltd. and Japan’s Dapeng Pharmaceutical Co., Ltd. Phase III clinical trials of pancreatic cancer in Taiwan and Japan are the largest clinical studies of pancreatic cancer in Asia at present. They include Taiwan University, Chang Gung, Wing, Ma, China, Changji, Chengda, Chi Mei , Gao Yi attached medical doctors have joined this clinical study. The results of this study confirm that oral TS-1 (Evans) has comparable efficacy to current standard gemcitabine in the treatment of advanced pancreatic cancer and has lower blood side effects; if combined with gemcitabine treatment, it can prolong the time of disease progression and can be effective. Reduce the tumor and relieve the clinical symptoms caused by the tumor. This research result of advanced pancreatic cancer was published in May 2013 in the internationally renowned journal Journal of Clinical Oncology. Taiwan now offers advanced and effective new treatment options for patients with advanced pancreatic cancer. Each year, it benefits about 1,500 patients with advanced pancreatic cancer.

On May 31, 2014 Pharmacyclics reported trial results of the first Phase III study (RESONATE, PCYC-1112-CA;NCT01578707), a head-to-head comparison of IMBRUVICA (ibrutinib) versus ofatumumab in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) (Press release Pharmacyclics, MAY 31, 2014, View Source [SID:1234500660]). Patients receiving IMBRUVICA realized a significant improvement in progression free survival (PFS), overall survival (OS) and overall response rate (ORR) as compared to patients receiving ofatumumab. The RESONATE data will be discussed today in the official Press Program by lead investigator Dr. John Byrd from The Ohio State University Medical Center at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL. This release corresponds to abstract LBA7008. IMBRUVICA is being jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.

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The RESONATE Phase III trial results have been published today in an online first edition of the New England Journal of Medicine. This study was also selected to be presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting in Milan on June 14, 2014 in the Presidential Symposium. This forum is set aside for abstracts of the highest impact and quality.

These Phase III study results show that IMBRUVICA significantly prolonged PFS in patients with relapsed/refractory CLL in comparison to those randomized to receive ofatumumab. Patients treated with IMBRUVICA experienced a 78% reduction in risk of progression or death versus patients receiving ofatumumab (HR 0.215, 95% CI, 0.146 to 0.317, p < 0.0001) per Independent Review Committee (IRC) evaluation. The median PFS for IMBRUVICA was not reached with a median time on study of 9.4 months. The median PFS for ofatumumab was 8.1 months. IMBRUVICA significantly prolonged OS compared with ofatumumab. IMBRUVICA reduced the risk of death by 57% (HR=0.434, 95% CI, 0.238 to 0.789; p < 0.0049) compared to the ofatumumab arm. This was observed despite a total of 57 patients who were initially randomized to ofatumumab crossing over to receive IMBRUVICA prior to the analysis. Patient characteristics were well balanced between arms: patients receiving IMBRUVICA had a median of 3 prior therapies with 32% deletion of the short arm of chromosome 17 (del17p), a mutation typically associated with poor prognosis, and 56% RAI stage III/IV (indicative of high risk CLL patients) versus patients receiving ofatumumab who had a median of 2 prior therapies with 33% del17p and 58% RAI stage III/IV.

ORR was significantly higher in patients receiving IMBRUVICA by both investigator and IRC evaluations. Investigator assessed overall response rate (including complete responses (CR), partial responses (PR) and partial responses with lymphocytosis (PR+L)) was 85 % for IMBRUVICA and 23% for patients receiving ofatumumab, evaluated based on the International Workshop on CLL (IWCLL) response criteria. The RESONATE study also had IRC evaluate sequential CT scans (performed per protocol, approximately 12 weeks apart) to assess and confirm response. With this analysis 63 % of IMBRUVICA patients achieved a partial response (PR or a PRL) compared to only 4 % of patients receiving ofatumumab (p < 0.0001). Significantly higher response rates were observed in the IMBRUVICA arm consistently across all subgroups by baseline disease risk factors, including those patients with del 17p or those whose disease was considered refractory to purine analogue therapy. Only 3% of the patients receiving IMBRUVICA experienced progressive disease as a best response versus 10% receiving ofatumumab as evaluated by IRC.

"In this patient population this is the first study ever, to demonstrate significant progression and overall survival benefits against an approved standard of care in CLL," said Dr. John Byrd*, Director, Division of Hematology, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital & Richard J. Solove Research Institute and lead investigator for RESONATE (PCYC 1102-CA). "As shown by the results presented today, IMBRUVICA is transforming the treatment for patients with CLL. It is an effective, patient friendly therapy that provides a real alternative to chemotherapy."

"The conclusion of IMBRUVICA’s first Phase III study is a major milestone on our company’s mission to achieving meaningful improvements in the quality and duration of life for patients," said Bob Duggan, CEO and Chairman of the Board of Pharmacyclics. "We are at the beginning of a transformational shift which will provide patients a new alternative to chemotherapy. Together, with our partner Janssen, we are proud of the accomplishments achieved to date. Establishing a large clinical program which currently consists of 11 Phase III studies, and a total of 45 ongoing trials in 8 histologies is a manifestation of our extraordinary confidence in IMBRUVICA."

The most commonly occurring adverse events independent of Grade (AEs in 20% or more of patients) were diarrhea (48% vs.18%), fatigue (28% vs. 30%), pyrexia (fever; 24% vs. 15%), nausea (26% vs.18%), anemia (23% vs. 17%) and neutropenia (22% vs. 15%). Hematologic adverse events that were Grade 3 or 4 in the RESONATE trial were neutropenia (decreased amount of white blood cells; 16% in the IMBRUVICA arm vs. 14% in the ofatumumab arm), thrombocytopenia (decrease in platelets in the blood; 6% vs. 4%), and anemia (5% vs. 8%). Atrial fibrillation of any grade was noted more frequently in patients receiving IMBRUVICA (5%versus 0.5% with ofatumumab), these events were manageable and lead to discontinuation for only 1 patient. There was no difference in major bleeding between the IMBRUVICA or ofatumumab arms (reported in 2 patients randomized to IMBRUVICA and 3 patients receiving ofatumumab). The incidence of grade 3 or higher infection was 24% for IMBRUVICA arm and 22% for the ofatumumab arm. Richter’s Transformation occurred in 2 patients in the IMBRUVICA arm and in 2 patients in the ofatumumab arm.

Patients receiving IMBRUVICA showed a discontinuation rate due to progressive disease, adverse events or death of 13%, with 86% of patients continuing on therapy. Patients receiving ofatumumab showed a discontinuation rate due to progressive disease, adverse events or death of 28%.

On May 31, 2014 Roche reported results from a Phase I open-label study that showed the investigational cancer immunotherapy MPDL3280A (anti-PDL1) shrank tumours (overall response rate) in 43 percent (13/30) of people previously treated for metastatic urothelial bladder cancer (UBC) whose tumours were characterised as PD-L1 (Programed Death Ligand-1) positive by a test being developed by Roche (Press release Hoffmann-La Roche, MAY 31, 2014, View Source [SID:1234500672]). Adverse events (AEs) were consistent with what has been previously reported for MPDL3280A. There were no severe (Grade 4-5) treatment related AEs.

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The FDA has granted MPDL3280A Breakthrough Therapy Designation. This designation is designed to expedite the development and review of medicines intended to treat serious diseases and to help ensure patients have access to them through FDA approval as soon as possible.

"Bladder cancer is the ninth most common cancer worldwide, for which there have been no new treatment advances in nearly 30 years, so we are pleased the FDA has granted breakthrough designation for MPDL3280A in metastatic bladder cancer," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "We are evaluating MPDL3280A in a broad range of tumours, and have begun pivotal studies that include a companion diagnostic test in lung and bladder cancers."

Full results of the study will be presented today at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) by Thomas Powles, M.D., clinical professor of Genitourinary Oncology, Barts Cancer Institute at the Queen Mary University of London, UK (Abstract #5011, Saturday, May 31, 3:36–3:48 P.M. Central Time).

About the Phase I MPDL3280A Study
The Phase I study is a single-arm, multi-center, open-label trial with a cohort of 68 people with previously treated, metastatic bladder cancer.
The study included 30 patients who were identified as PD-L1 positive (immunohistochemistry [IHC] 2/3) using an investigational PD-L1 diagnostic test being developed by Roche.
After six weeks of follow-up, the objective response rate (ORR) as measured by RECIST criteria was 43 percent (13/30), and after 12 weeks, ORR was 52 percent (13/25) in people with PD-L1-positive tumours.
A complete response (no radiographic evidence of tumour) was observed in 7 percent of PD-L1-positive patients (2/30).
The ORR was 11 percent (4/35) in people whose tumours were identified as PD-L1-negative (IHC 0/1) by our investigational test.
People in the study experienced a median time to response of 42 days.
Treatment-related Grade 3 AEs occurred in 4 percent (3/68) of people in the study and included weakness (asthenia; 2 percent), low platelet count (thrombocytopenia; 2 percent) and low phosphate levels (blood phosphorus decrease; 2 percent).
The most common AEs observed to date occurring in more than 5 percent of patients were decreased appetite (12 percent), fatigue (12 percent), nausea (12 percent), fever (pyrexia; 9 percent) and weakness (asthenia; 7 percent).

On May 30, 2014 Deciphera Pharmaceuticals reported the initiation of a Phase 1 clinical trial of its MET/TIE2/VEGFR2/TRK inhibitor altiratinib (DCC-2701) (Press release Deciphera Pharmaceuticals, MAY 30, 2014, View Source [SID:1234500714]). The Phase 1 trial will evaluate the safety, tolerability and initial efficacy of altiratinib in cancer patients with solid tumors. Altiratinib has been shown to exhibit high potency and selectivity for inhibiting MET, TIE2, VEGFR2, and TRK kinases in preclinical studies. A companion diagnostic assay will also be co-developed during the course of clinical studies.

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In preclinical cancer models, altiratinib has shown impressive activity against multiple tumors including melanoma, ovarian, glioblastoma, colorectal, gastric and breast cancers.
"We are pleased to advance altiratinib into clinical development based on the encouraging preclinical data demonstrated to date," says Michael D. Taylor, PhD, Deciphera’s President and Chief Executive Officer. "With its balanced inhibition of key kinase mechanisms, including MET, TIE2, VEGFR2 and TRK, altiratinib was designed to address both tumor cells and the tumor microenvironment by providing high potency and inhibition against cancer cells, metastases, and invasiveness. We look forward to reporting on our progress with altiratinib, which has the potential to provide an important new option for cancer patients with solid tumors."